ArticleMolecular and cellular biology2005
mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 152 citations in OpenAlex.
- Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity.British journal of cancer · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Menin-driven mTOR signaling sustains taxane resistance in CRPC and reveals a targetable vulnerability for combination therapy.Cell communication and signaling : CCS · 2025Article
- Article
- TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma.Acta neuropathologica communications · 2023Article
- Machine learning identification of cuproptosis and necroptosis-associated molecular subtypes to aid in prognosis assessment and immunotherapy response prediction in low-grade glioma.Frontiers in genetics · 2022Article
- Overcoming TRAIL Resistance for Glioblastoma Treatment.Biomolecules · 2021Review
- RPP25 as a Prognostic-Related Biomarker That Correlates With Tumor Metabolism in Glioblastoma.Frontiers in oncology · 2021Article
- Tumoricidal stem cell therapy enables killing in novel hybrid models of heterogeneous glioblastoma.Neuro-oncology · 2019Article
- TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.Life science alliance · 2019Article
- ITCH-dependent proteasomal degradation of c-FLIP induced by the anti-HER3 antibody 9F7-F11 promotes DR5/caspase 8-mediated apoptosis of tumor cells.Cell communication and signaling : CCS · 2019Article
- mTOR signalling pathway - A root cause for idiopathic autism?BMB reports · 2019Review
- Targeting KPNB1 overcomes TRAIL resistance by regulating DR5, Mcl-1 and FLIP in glioblastoma cells.Cell death & disease · 2019Article
- TRAIL pathway targeting therapeutics.Expert review of precision medicine and drug development · 2018Article
- Article
- Rapamycin Treatment for Benign Multicystic Peritoneal Mesothelioma: A Rare Disease with a Difficult Management.The American journal of case reports · 2017Article
- Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.Breast cancer research and treatment · 2017Article
- Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma.Molecular oncology · 2016Article
- Systemically administered AAV9-sTRAIL combats invasive glioblastoma in a patient-derived orthotopic xenograft model.Molecular therapy oncolytics · 2016Article
- Inhibition of Notch1 signaling overcomes resistance to the death ligand Trail by specificity protein 1-dependent upregulation of death receptor 5.Cell death & disease · 2015Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor-selective, proapoptotic, death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a mediator of antitumor drug activity and in itself is a promising agent for the treatment of human malignancies. Like many tumors, however, glioblastoma multiforme (GBM), the most fatal form of glioma, exhibits a range of TRAIL sensitivity, and only a small percentage of GBM tumors undergo TRAIL-induced apoptosis. We here show that TRAIL resistance in GBM is a consequence of overexpression of the short isoform of the caspase-8 inhibitor, c-FLICE inhibitory protein (FLIP(S)), and that FLIP(S) expression is in turn translationally enhanced by activation of the Akt-mammalian target of rapamycin (mTOR)-p70 S6 kinase 1 (S6K1) pathway. Conversely, pharmacologic or genetic inhibition of mTOR, or the mTOR target S6K1, suppresses polyribosomal accumulation of FLIP(S) mRNA, FLIP(S) protein expression, and TRAIL resistance. In archived material from 12 human GBM tumors, PTEN status was a predictor of activation of the Akt-mTOR-S6K1 pathway and of FLIP(S) levels, while in xenografted human GBM, activation status of the PTEN-Akt-mTOR pathway distinguished the tumors inherently sensitive to TRAIL from those which could be sensitized by the mTOR inhibitor rapamycin. These results define the mTOR pathway as a key limiter of tumor elimination by TRAIL-mediated mechanisms, provide a means by which the TRAIL-sensitive subset of GBM can be identified, and provide rationale for the combined use of TRAIL with mTOR inhibitors in the treatment of human cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.